Normalized Glucose Levels in Type 2 Diabetes With Carbohydrate or Caloric Restriction (CarborCal)

Normalized Glucose Levels in Type 2 Diabetes With Carbohydrate or Caloric Restriction: a Randomized Controlled Trial (CarborCal)

The scientific evidence for diet recommendation to patients with type 2 diabetes is insufficient. Poor diet quality is a principal cause of obesity, which strongly increases the risk of secondary diseases such as type 2 diabetes (T2D), cardiovascular disease and cancer. A newly published study the DiRECT trial demonstrated startlingly that diet-induced weight loss of 15 kg can effectively reverse T2D in most patients. The concept of reversibility, into remission, of T2D with diet is new, and we urgently need to document the most optimal dietary strategies. In a multicenter dietary intervention of 650 patients with T2D, we plan to compare to diets in regards to remission rate for T2D. One diet will be a low-carbohydrate diet. Participants in this group can eat as much food as they like but are recommended to keep the carbohydrate amount very low (maximum 30 gram per day) during the first 3 months of the study. Thereafter they can increase the carbohydrate amount (up to 80 g carbohydrates per day) during 12 months. The other group will be on a low caloric diet. This group will have dietary replacement diet containing 800-850 KCal/day for 3 months. Thereafter will participant in this group be divided in two subgroups: one will continue with low fat diet and the other subgroup will continue on low carbohydrate diet (maximum 80-gram carbohydrate per day) for 12 months. The aim of the study is to evaluate if Low carbohydrate diet can generate and/or maintain an equal remission rate as with the low caloric diet leading to 15 kg weight loss. Each center will also conduct mechanistic studies. Finally, we will translate our new insights into innovative electronic tools to support preventive as well as therapeutic healthy eating.

Data collection, measurements and analysis: Anthropometric data and blood , urin and feaces samples will be collected at visits at the clinic at baseline and after 3 months (initial weight loss and remission) months (continued weight loss and remission), and 15 months (weight maintenance). For security reason Hb1c and lipid status will be analyzed every 3 month. For Standardized measurement protocols, instruments (e.g., for anthropometrics), collection tubes, etc. will be used. HbA1c, glucose, lipids and other standard biochemical variables will be measured directly on the day of the visit at the laboratories, or, for substances sensitive to batch effects (e.g., serum insulin), after collection and freezing at -80°C. Samples that are not analyzed immediately will be stored in a biobank for later use. The study will be performed in accordance with GCP. Body composition: Before, at 3 and 15 month, body composition will be measured using bio impedance (BIA) Diet effect on insulin release: At baseline and after 3 and 15 months, the B-cell capacity of insulin release will be investigated by a glucagon stimulated test (GSCT). GSCT will be performed by collecting blood samples before and 6 minutes after an intravenous injection of 0.5 mg glucagon. Secured serum samples will be analysed for C-peptide, insulin and proinsulin. Development of user-friendly electronic tools for healthy eating: An online database/platform with hundreds of recipes will be prepared. The platform will furthermore include online support for both cooking and behavioral modification, interactive communication through, e.g., a chat service and weekly newsletters with reminders, educational videos covering topics such as how to prepare foods, meal planning, food addiction, food and mood, and dining out. Participants will be asked to fill in 3 days diet register online on the platform before the start of the study and after 3 and 15 months. Questionnaires: Questionnaires EQ-5DL, AUDIT and questionaries for satisfaction with the diet will be handed to participants before the start of the study and after 3 and 15 months. Determination of diet effect on T2D remission: An intention-to-treat analysis using appropriate statistical models, as well as analyses for each sex separately, will be performed. The frequency of requiring "rescue plans" for relapse management in those with weight regain, will be collected.

Participants will have acces to a plattform with recepies containing 30 g carbohydrate / day during the first three months and thereafter recepies containing 80 g carbohydrate/ day during the remaining 12 months

Participants will be asked to by low caloric diet replacement containing 850 kCal/day during the first 3 months, aiming for a weight loss of 10 kg during and thereafter will have access to recepies containing less calorie for weight maintenance during the remaining 12 months

Inclusion Criteria: HbA1c > 48 mmol/mol (with or without medical treatment); less than 6 years since the diagnosis of T2D BMI ≥ 27 kg/m2 (≥ 25 kg/m2 for Asians). Exclusion Criteria: Insulin deficiency. HbA1c concentration of 12% or more (≥108 mmol/mol), treatment with sulphonyl urea or sodium-glucose-cotrasporter2-inhibitor (SGL2-i), myocardial infarction within the previous 6 months, severe or unstable heart failure other severe diseases including cancer, psychiatric/eating disorders, severe depression - substance abuse, conditions that may affect the ability of patients to participate in the study